Highly corrosive to soft tissue; severe damage to soft tissues if extravasation occurs.100 Contracture of the arms has been reported.100 (See Local Effects under Cautions.)

Administer only under the supervision of a qualified clinician experienced in the use of cancer chemotherapeutic agents.100

Introduction

Antineoplastic agent; an actinomycin antibiotic produced by Streptomyces parvullus.100

Uses for Cosmegen

Wilms’ Tumor

In children with Wilms’ tumor, used in combination regimens (e.g., with vincristine with or without doxorubicin) as an adjunct to surgery with or without radiation therapy.100101103 The best combination or sequential therapy to achieve maximum response and duration of survival has not been established and comparative efficacy is continually being evaluated.100103

Generally should not be administered concomitantly with radiation therapy in the treatment of Wilms’ tumor.100103 (See Toxicity Potentiation with Concomitant Radiation Therapy under Cautions.)

Rhabdomyosarcoma

Component of various chemotherapeutic regimens as an adjunct to surgery with or without radiation therapy; however, the best combination or sequential therapy to achieve maximum response and duration of survival has not been established and comparative efficacy is continually being evaluated.100101103104

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Ewing’s Sarcoma

Has been used in combination chemotherapy for treatment of Ewing’s sarcoma;100 however, other regimens currently are preferred.101105

Trophoblastic Neoplasms

Treatment (alone or as a component of various chemotherapeutic regimens) of trophoblastic neoplasms (choriocarcinoma, chorioadenoma destruens) in women.100101106

Dactinomycin alone is generally reserved for patients whose tumors develop resistance or do not respond to methotrexate or in patients with impaired hepatic or renal function with increased risk of methotrexate toxicity.106

Combination therapy with methotrexate and cyclophosphamide (MAC regimen) has been used for treatment of metastatic gestational trophoblastic tumors that are refractory to single-drug therapy.101106

Combination therapy with etoposide, methotrexate, cyclophosphamide, and vincristine (EMA-CO) is commonly used in patients with poor-prognosis metastatic gestational trophoblastic tumors.101106

Testicular Cancer

Used in combination with vinblastine, bleomycin, cyclophosphamide, and cisplatin (VAB-6) for the treatment of advanced nonseminomatous testicular carcinoma.100107 The best combination or sequential therapy has not been established and comparative efficacy is continually being evaluated.107

Solid Tumors

Used alone or in combination with other chemotherapeutic agents by regional isolation perfusion as an adjunct to surgery or as palliative therapy alone in the treatment of locally recurrent or locoregional solid tumors (sarcomas, carcinomas, and adenocarcinomas).100

Avoid extravasation; extremely irritating to tissues.100 Pain and burning or stinging sensation during IV administration may be a symptom, but extravasation may occur without these symptoms and even when blood returns well on aspiration of the infusion needle.100 If manifestations of extravasation occur, immediately stop administration and restart at another site; apply ice intermittently to affected area for 15 minutes 4 times daily for 3 days. 100 Because of the progressive nature of extravasation reactions, close observation and plastic surgery consultation recommended.100 Blistering, ulceration, and/or persistent pain are indications for wide excision surgery, followed by split-thickness skin grafting.100 (See Local Effects under Cautions.)

Prepare and handle cautiously (by trained nonpregnant personnel); use protective equipment (e.g., latex gloves, protective eyewear) and wash hands after removal of latex gloves.100 Avoid exposure by inhalation or by direct contact of the skin or mucous membranes.100 If drug powder or solution comes in contact with skin or mucosa, immediately irrigate affected area with water for ≥15 minutes; flush affected eye(s) with water or saline for ≥15 minutes and obtain prompt ophthalmologic consultation.100 Remove contaminated clothing and shoes; destroy clothing and and thoroughly clean shoes before reuse.100 (See Toxicity and Adequate Patient Monitoring under Cautions.)

Administer desired dose directly into any suitable vein or preferably into tubing or sidearm of a freely flowing IV infusion to reduce the risk of severe local reactions.100 (See Local Effects under Cautions.)

Following injection, flush vein with the running IV solution for 2–5 minutes and/or inject 5–10 mL of IV solution into sidearm to flush any remaining drug from the tubing.a

For direct IV injection, withdraw dose from the vial with one sterile needle and use another sterile needle for injection into vein.100

Do not use an inline cellulose ester membrane filter during administration.a

Reconstitution

Use strict aseptic technique since drug product contains no preservative.100

Reconstitute vial containing 500 mcg of dactinomycin powder with 1.1 mL of sterile water for injection without preservatives, to provide a solution containing 500 mcg/mL.100

Do not use diluents with preservatives (benzyl alcohol or parabens) which may cause precipitation.100

Dilution

Reconstituted solution may be added to IV infusions of 0.5% dextrose or 0.9% sodium chloride injection.100

Rate of Administration

For direct IV injection, administer desired dose over a few minutes directly into any suitable vein.a

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; teratogenicity and embryotoxicity demonstrated in animals.100 Avoid pregnancy during therapy.100 If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.100

Immunosuppression

Do not administer at or near the time of infection with chickenpox or herpes zoster.100 Risk of severe and possibly fatal generalized disease.100

Use with extreme caution in patients with impaired bone marrow function.a

GI Effects

Nausea and vomiting; generally occur within hours of administration and last up to 24 hours.100a Antiemetics may be effective in preventing or treating nausea and vomiting.100a

Risk of stomatitis or diarrhea; if stomatitis or diarrhea develops, discontinue therapy until symptoms resolve. 100

Hepatic Effects

Potentially fatal hepatic failure and hepatic veno-occlusive disease reported.100 Veno-occlusive disease may be associated with intravascular clotting disorder and multiorgan failure and may be fatal, particularly in children <4 years of age.100

General Precautions

Toxicity and Adequate Patient Monitoring

Highly toxic drug with a low therapeutic index; therapeutic response is not likely to occur without some evidence of toxicity.100a Handle and administer cautiously; administer only under the supervision of qualified clinician experienced in the use of cancer chemotherapy agents.100 (See IV Administration under Dosage and Administration.)

Toxicity Potentiation with Concomitant Radiation Therapy

Appears to potentiate effects of radiation therapy.100 Severe reactions possible if high doses of both dactinomycin and radiation are used or if patient is especially sensitive to such combination therapy.100

Erythema at the site of irradiation may occur early in normal skin and buccal and pharyngeal mucosa and may be followed rapidly by hyperpigmentation and/or edema, desquamation, vesiculation, and rarely necrosis.100a

Hepatomegaly, elevated serum AST concentrations, and ascites reported in the first 2 months after radiation therapy in patients with right-sided Wilms’ tumor; administer dactinomycin with particular caution in the first 2 months after radiation therapy.100a Do not administer concomitantly with radiation therapy for treatment of Wilms’ tumor unless benefit outweighs risk.100103

Specific Populations

Pregnancy

Lactation

Not known whether dactinomycin is distributed into human milk.100 Discontinue nursing or the drug.100

Pediatric Use

Increased incidence of adverse effects in infants; use only in infants older than 6–12 months of age.100

Increased incidence of fatal veno-occlusive disease in children <4 years of age.100 (See Hepatic Effects under Cautions.)

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults; consider the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly.100

Actions

Mechanism(s) of antineoplastic action not fully understood; appears to inhibit DNA-dependent RNA synthesis by forming a complex with DNA by intercalating with guanine residues and impairing the template activity of DNA.100a

Also inhibits protein and DNA synthesis, but less extensively and at higher concentrations of dactinomycin than are needed to inhibit RNA synthesis.a

Advice to Patients

Importance of patients informing clinicians immediately if any stinging or burning occurs at IV injection site during administration.100

Importance of women informing clinicians immediately if they are or plan to become pregnant or plan to breast-feed; necessity for clinicians to advise women to avoid pregnancy during therapy and advise pregnant women of risk to the fetus.100

Importance of patients informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.100

Importance of informing patients of other important precautionary information.100 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.